The Other Side of Covid-19 Immunity

Not all immunity research has to do with antibodies

This week, research suggesting that antibodies to Covid-19 wane quickly after infection raised concerns about immunity to the coronavirus. Throughout the pandemic, much of the conversation about immunity has focused on antibodies: using antibody tests to look for them, filtering them out of convalescent plasma, and hoping that a vaccine will elicit enough of them. If antibodies disappear soon after recovery, they aren’t going to be that helpful.

But as I wrote yesterday in Elemental, antibodies are only one side of the immunity story. The other side has to do with T cells. Unlike antibodies, which fight an infection by targeting the pathogen itself, some T cells (called “killer T” cells) can do so by attacking the cells that are infected, and others (called “helper T” cells) help coordinate the attack on invaders and spur the production of more antibodies.

T cells in general haven’t been talked about as much, but they’re the focus of a lot of promising Covid-19 research. If antibodies end up being insufficient for fighting the coronavirus, T cells may be able to pick up the slack or offer complementary support. Helper T cells, in particular, are getting a lot of attention in Covid-19 research, in part because of their potential to help boost the production of waning antibodies.

So far, a lot of T-cell research has focused on figuring out whether people who have Covid-19 have helper T cells that can recognize SARS-CoV-2, or at least parts of it. As early as April, researchers from Berlin identified helper T cells in people hospitalized with Covid-19. The T cells they found specifically recognized the coronavirus’s increasingly notorious spike protein, which it uses to get into a cell. The researchers posted their preprint (a paper that hasn’t yet gone through the critical process of peer review) to the server medRxiv.

In May, research published in Cell showed similar findings: 10 people who had Covid-19 all had helper T cells that recognized the spike protein as well as other proteins on SARS-CoV-2. Even more notable was their finding that about 40% to 60% of people who never had a Covid-19 infection also had helper T cells that could recognize the coronavirus. This suggested that when people get exposed to other coronaviruses, like the ones that cause the common cold, their helper T cells that get activated can also recognize parts of SARS-CoV-2.

Research continued to trickle in through June, including a bioRxiv preprint from a team from Sweden’s Karolinska Institutet and Karolinska University Hospital showing in a small study that even people with mild or totally asymptomatic Covid-19 cases had T cells that recognized SARS-CoV-2. Co-author Marcus Buggert, PhD, however, told the BBC that further work was needed to find out whether these T cells could actually fight off a future infection. Today, new research published in Nature showed further evidence that people who get sick with Covid-19 develop a T cell response and that people who have never been exposed to the coronavirus can have T cells that recognize parts of the virus, too.

It’s crucial to understand that the mere presence of T cells, either killer T or helper T, doesn’t guarantee immunity, and the same goes for antibodies. As it becomes clearer that the coronavirus does elicit a T cell response in people who are sick, scientists must now figure out whether those T cells can do the things we need them to do — like spur the production of antibodies through a vaccine, or attack SARS-CoV-2 upon future reinfections. There’s a lot that’s still unknown about this branch of the immune system as it relates to Covid-19, but it’s clearly a great option to have on the table.